Coupling of dopamine receptors to G proteins: Studies with chimeric D2/D3 dopamine receptors

Tal Ilani, C. Simone Fishburn, Berta Levavi-Sivan, Shari Carmon, Lily Raveh, Sara Fuchs*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

D2 and D3 dopamine receptors belong to the superfamily of G protein-coupled receptors; they share a high degree of homology and are structurally similar. However, they differ from each other in their second messenger coupling properties. Previously, we have studied the differential coupling of these receptors to G proteins and found that while D2 receptor couples only to inhibitory G proteins, D3 receptor couples also to a stimulatory G protein, Gs. We aimed to investigate the molecular basis of these differences and to determine which domains in the receptor control its coupling to G proteins. For this purpose four chimeras were constructed, each composed of different segments of the original D2 and D3 receptors. We have demonstrated that chimeras with a third cytoplasmic loop of D2 receptor couple to Gi protein in a pattern characteristic of D2 receptor. On the other hand chimeras containing a third cytoplasmic loop of D3 receptor have coupling characteristics like those of D3 receptor, and they couple also to Gs protein. These findings demonstrate that the third cytoplasmic loop determines and accounts for the coupling of dopamine receptors D2 and D3 to G proteins.

Original languageAmerican English
Pages (from-to)47-56
Number of pages10
JournalCellular and Molecular Neurobiology
Volume22
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported in part by research grants from The Abramson Family Foundation and from the Edith C. Blum Foundation.

Keywords

  • Adenylate cyclase
  • Chimeric receptor
  • Dopamine receptors
  • G protein
  • Signal transduction

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